Filgrastim (r-metHuG-CSF) and its potential use in the reduction of radiation-induced oropharyngeal mucositis: an interim look at a randomized, double-blind, placebo-controlled trial.

We wished to determine if filgrastim administration to chemotherapy/radiation therapy-naive patients receiving external-beam irradiation for head-and-neck malignancies would reduce the incidence and severity of oral/oropharyngeal mucositis. Patients were randomized to receive subcutaneous injections of either filgrastim or placebo beginning on day 1 of radiation and continuing daily throughout treatment. Study medication was titrated to keep the neutrophil count between 10 x 10(9) and 30 x 10(9)/l. The left and right buccal mucosa, hard palate, and posterior pharyngeal wall were scored weekly, by a blinded evaluator using two different scales, and the most severe score per week was used in data analysis. Fourteen of a planned 54 patients were randomized (8 filgrastim, 6 placebo), and were evaluable for a planned interim analysis. No statistically significant between-group differences were seen in mean worst scores across time using repeated measures analysis of variance (Hickey, p = 0.231; WHO, p= 0.288). At almost all timepoints, however, the worst mean scores were lower in patients treated with filgrastim compared with those in patients treated with placebo, and the number of severe (i.e., grade 3) mucositis scores was significantly lower in the filgrastim-treated group. Filgrastim may decrease the severity of radiation-induced oral/oropharyngeal mucositis.

Radiation tolerance of transverse rectus abdominis myocutaneous-free flaps used in immediate breast reconstruction.

The authors determine the effects of postoperative radiation therapy on flap and local control outcomes in patients who have undergone immediate transverse rectus abdominis myocutaneous (TRAM)-free flap reconstruction after modified radical mastectomy for locally advanced breast cancer. Details of surgery, chemotherapy, and radiation therapy for 21 patients who had undergone immediate TRAM-free flap reconstruction after modified radical mastectomy were gathered retrospectively. The outcomes examined were flap complications, overall cosmesis, and local recurrence rate. Radiation therapy was indicated for large primary tumors (T3-T4), close or positive margins, or extensive nodal disease. With a mean follow-up interval of 19 months, there have been no flap complications or losses. Cosmesis was rated as excellent by 60% of patients, good by 30%, and fair by the remaining 10%. Three patients thought that radiation had improved cosmesis, one noted worse cosmesis, and the remainder thought it had no effect on cosmesis. The local control rate was 86%. Postreconstruction irradiation of TRAM-free flaps used in immediate reconstruction for locally advanced breast cancer appears safe and cosmetically acceptable.

Concomitant pilocarpine during head and neck irradiation is associated with decreased posttreatment xerostomia.

PURPOSE: To retrospectively compare subjective postirradiation xerostomia scores of patients who received concomitant oral pilocarpine during radiotherapy for head and neck cancer and 3 months thereafter with those of similar cohorts who did not receive pilocarpine. METHODS AND MATERIALS: Subjective xerostomia was assessed using a visual analog scale xerostomia questionnaire that measured oral dryness, oral comfort, difficulty with sleep, speech, and eating. The concomitant pilocarpine group had both parotid glands in the initial field treated to at least 45 Gy and received 5 mg pilocarpine hydrochloride four times per day (q.i.d.) beginning on the first day of radiotherapy and continuing for 3 months after completion of radiation. The control cohort had also received at least 45 Gy to both parotid glands and had not received pilocarpine at the time of evaluation. Scores on the visual analog scale were averaged and compared using the Student's t-test. RESULTS: Seventeen patients who received concomitant pilocarpine during head and neck irradiation and 18 patients who had not been treated with pilocarpine were available for follow-up. The mean intervals between completion of radiation and evaluation of xerostomia were 17 months and 16 months, respectively. Only one of the pilocarpine-treated patients was still taking pilocarpine at the time of evaluation. For each of the individual components of xerostomia scored on the visual analog scale, as well as the composite of all components, the group that had received oral pilocarpine during radiation had significantly less xerostomia (p < 0.01 for each). CONCLUSIONS: The use of 5 mg oral pilocarpine q.i.d. during radiotherapy for head and neck cancer and 3 months thereafter was associated with significantly less subjective xerostomia than that reported by a similar cohort of patients who had not received pilocarpine. The continued use of pilocarpine does not appear to be necessary to maintain this benefit in most patients.

Angiosarcoma. A report of 67 patients and a review of the literature.

BACKGROUND: Angiosarcomas (AS) are rare, aggressive tumors. Optimal treatment has not been well defined. The authors undertook a retrospective review of patients seen at their institution with the intent of identifying prognostic factors and optimal treatment strategies. METHODS: Between 1955 and 1990, 67 patients with AS were seen at the University of California, at Los Angeles Medical Center. Follow-up ranged from 1 to 173 months with a median of 30 months. RESULTS: The overall prognosis was poor. The actuarial 2- and 5-year disease free survivals (DFS) were 44% and 24%, respectively. Of 52 recurrences after primary treatment, 81% (42 of 52) had a component of local failure. Twenty-eight patients had developed distant metastases at last follow-up. Of patients who received surgery (S) and radiation therapy (RT), with or without chemotherapy (CT), 5-year actuarial DFS was 43%, compared with 17% for patients who underwent S +/- CT as initial treatment (P = 0.03). Only 9% of patients (1 of 11) treated with RT +/- CT were rendered free of disease. CONCLUSIONS: Patients with AS usually present with high grade histology, and with multifocal disease. There is a propensity for both local recurrence and distant metastases. Our results and a review of the literature, suggest that S plus RT offers the best chance for long term control of this aggressive tumor. The role of CT remains undefined.

Angiosarcoma of the head and neck. The UCLA experience 1955 through 1990.

Between 1955 and 1990, 28 patients with angiosarcoma of the head and neck were seen at UCLA Medical Center, Los Angeles, Calif. Half the lesions arose on the scalp; the remainder occurred in the soft tissues of the face and neck. Nine patients presented with multifocal disease. Follow-up ranged from 3 to 159 months, with a median of 32 months. The overall prognosis was poor, with a 5-year disease-free survival of 26% (7/27 patients). Of 21 patients having recurrences after primary treatment, 90% (19/21 patients) had a component of local failure. Distant metastasis had developed in nine patients at last follow-up. Of patients treated initially with surgery alone, 8% (1/12 patients) remain disease free vs 67% (4/6 patients) who received postoperative radiation therapy, with or without chemotherapy. Only one (14%) of seven patients treated primarily with radiation therapy with or without chemotherapy was rendered disease free. Angiosarcoma usually presents with high-grade histologic features and frequently with multifocal disease. There is propensity for both local recurrence and distant metastasis. Our results and a review of the literature suggest that combined modality therapy offers the best chance for long-term control in patients with angiosarcoma of the head and neck.

Differential effects of Pitressin on blood flow and oxygen extraction in canine vascular beds.

Physiologic studies in dogs have been performed with an intravascular flow/diameter sensor which can be introduced directly into the aorta or its branch vessels through a percutaneous radiologic catheter. These studies have focused upon attempts to devise a clinically practical means to protect the small intestine from radiation damage during therapy of abdominal and pelvic malignant tumors. The effects on superior mesenteric, renal, and lower extremity blood flows of controlled infusions of Pitressin given directly into the superior mesenteric artery or into a peripheral vein have been measured. In addition, using these regional flow measurements and arteriovenous differences in oxygen content, regional tissue oxygen extraction rates during Pitressin infusions have also been estimated. The data show that intravenous Pitressin at an infusion rate of 0.0124 U/kg/min may be almost as effective as Pitressin given directly into the superior mesenteric artery in lowering superior mesenteric blood flow (40%-70% reduction for intravenous, 50%-70% for direct arterial infusions) and intestinal oxygen extraction (20%-40% reduction for intravenous, 40%-50% for direct arterial infusions). The effects of Pitressin at similar dose rates on the kidney and the lower extremity are less reproducible, and it is possible that relatively selective radiation protection of the intestine using systemic (intravenous) infusions of Pitressin during abdominopelvic radiotherapy might be achievable.